FDA Accepts Two Applications for Pembrolizumab in Triple-Negative Breast Cancer
Posted: Tuesday, August 4, 2020
On July 30, the U.S. Food and Drug Administration (FDA) granted Priority Review for a supplemental Biologics License Application for the use of pembrolizumab with chemotherapy for patients with locally recurrent, unresectable, or metastatic triple-negative breast cancer whose tumors express PD-L1. The FDA also granted a standard review of a supplemental Biologics License Application for pembrolizumab in combination with chemotherapy as neoadjuvant therapy or as a single agent as adjuvant therapy after surgery for patients with high-risk early-stage triple-negative breast cancer.
The Priority Review designation for pembrolizumab was based on the double-blind phase III KEYNOTE-355 clinical trial. A total of 847 patients with a disease-free interval of 6 months or de novo metastatic disease were eligible for the study. Approximately 38% of patients had tumors expressing PD-L1 at a combined positive score (CPS) of 10 or greater. Patients received 200 mg of pembrolizumab for 3 weeks or a placebo along with investigator’s choice of chemotherapy. Patients receiving pembrolizumab and chemotherapy who had a CPS score of at least 10 experienced significant and clinically meaningful improvement in progression-free survival.
The standard review for pembrolizumab for high-risk early-stage triple-negative breast cancer was based on the double-blind KEYNOTE-522 clinical trial. The study randomly assigned 1,174 patients with triple-negative breast cancer to receive 3 weeks of pembrolizumab or a placebo plus weekly doses of paclitaxel and carboplatin (or every 3 weeks) for four cycles. This was followed by pembrolizumab or a placebo plus cyclophosphamide and either doxorubicin or epirubicin every 3 weeks for four cycles as neoadjuvant therapy prior to surgery. Then, nine cycles of pembrolizumab or a placebo was administered every 3 weeks as adjuvant therapy after surgery.
Results showed a statistically significant increase in pathologic complete response with neoadjuvant pembrolizumab plus chemotherapy in patients with early-stage triple-negative breast cancer, regardless of PD-L1 expression. Ongoing data also show a favorable trend for event-free survival.